Intellectual disability (ID) is a neurodevelopmental disorder characterized by limitations in both intellectual and behavioral functioning. It can occur in non‐syndromic and syndromic forms involving multiple organs. While the majority of genetic variants linked to ID are de novo, inherited variants are also detected in some forms. Here, we report a consanguineous Lebanese family presenting with an autosomal recessive syndromic ID characterized by neurodevelopmental delay, mild dysmorphic features, hearing impairment and endocrine dysfunction. Whole exome sequencing enabled the detection of the homozygous nonsense mutation in BOD1, p.R151X, in the proband. BOD1 is required for chromosomes biorientation during cell division. It also contributes to the regulation of cell survival and to the modulation of fatty acid metabolism. Another nonsense mutation in BOD1 was linked to ID in a consanguineous Iranian family. This is the second report of BOD1 mutations in humans and the first in a syndromic ID including gonadal dysfunction and high‐frequency hearing impairment. Our findings confirm the involvement of BOD1 in cognitive functioning and expand the clinical spectrum of BOD1 deficiency.

中文翻译：

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患有综合征性智力障碍的黎巴嫩患者的BOD1基因纯合终止增益突变。

智力障碍（ID）是一种神经发育障碍，其特征是智力和行为功能受到限制。它可以以涉及多个器官的非综合征和综合征形式发生。虽然大多数与ID相关的遗传变异都是从头开始的，但也可以某些形式检测到遗传变异。在这里，我们报告了一个近亲黎巴嫩家庭，其特征是具有神经发育延迟，轻度畸形，听力障碍和内分泌功能障碍的常染色体隐性遗传综合征。整个外显子组测序可检测BOD1中的纯合性无义突变，先证者中的p.R151X。BOD1是细胞分裂过程中染色体生物定向所必需的。它还有助于调节细胞存活率和调节脂肪酸代谢。BOD1的另一个无意义的突变与伊朗近亲家庭的ID有关。这是人类BOD1突变的第二次报告，也是包括性腺功能障碍和高频听力障碍在内的综合症ID的首次报告。我们的发现证实了BOD1参与认知功能并扩大了BOD1缺乏症的临床范围。